Bottom Line:
These changes were found associated with the deterioration of encoding action potentials in cortical neurons.In addition, MDA increased the ratio of γ-aminobutyric acid to glutamate in turtle's brain, as well as the sensitivity of GABAergic neurons to inputs compared to excitatory neurons.Therefore, MDA, as a metabolic product in the brain, may weaken cerebral function during carbonyl stress through breaking the homeostasis between excitatory and inhibitory neurons.

ABSTRACTThe levels of malondialdehyde (MDA) are high in the brain during carbonyl stress, such as following daily activities and sleep deprivation. To examine our hypothesis that MDA is one of the major substances in the brain leading to fatigue, the influences of MDA on brain functions and neuronal encodings in red-eared turtle (Trachemys scripta) were studied. The intrathecal injections of MDA brought about sleep-like EEG and fatigue-like behaviors in a dose-dependent manner. These changes were found associated with the deterioration of encoding action potentials in cortical neurons. In addition, MDA increased the ratio of γ-aminobutyric acid to glutamate in turtle's brain, as well as the sensitivity of GABAergic neurons to inputs compared to excitatory neurons. Therefore, MDA, as a metabolic product in the brain, may weaken cerebral function during carbonyl stress through breaking the homeostasis between excitatory and inhibitory neurons.

pone-0015325-g003: The comparison of inter-spike intervals (ISI) and the standard deviation of spike timing (SDST).ISI and SDST of pyramidal neurons (PN) and interneurons (IN) before and after 20 µM MDA treatments as indicated (* p<0.05, **p<0.01).

Mentions:
To understand cellular mechanisms underlying MDA-induced sleep-like EEG and fatigue-like behaviors, we examined the influences of MDA on spike encodings in cortical neurons. Whole-cell patch clamp was conducted at pyramidal neurons and fast-spiking interneurons in cortical slices of turtles, and MDA (20 µM) was washed onto the brain slices by adding it into perfuse solution. MDA increased ISI of sequential spikes in pyramidal neurons and interneurons, especially in interneurons (Fig. 3; Table S1). As inter-spike intervals are mainly controlled by refractory periods [33], we tested if MDA prolonged ARP. The measurements of ARP were done by giving multiple pulses (Methods for details; Table S2). These results indicate that MDA attenuates the capacity of encoding sequential spikes through the prolongation of absolute refractory periods (Fig. 4).

pone-0015325-g003: The comparison of inter-spike intervals (ISI) and the standard deviation of spike timing (SDST).ISI and SDST of pyramidal neurons (PN) and interneurons (IN) before and after 20 µM MDA treatments as indicated (* p<0.05, **p<0.01).

Mentions:
To understand cellular mechanisms underlying MDA-induced sleep-like EEG and fatigue-like behaviors, we examined the influences of MDA on spike encodings in cortical neurons. Whole-cell patch clamp was conducted at pyramidal neurons and fast-spiking interneurons in cortical slices of turtles, and MDA (20 µM) was washed onto the brain slices by adding it into perfuse solution. MDA increased ISI of sequential spikes in pyramidal neurons and interneurons, especially in interneurons (Fig. 3; Table S1). As inter-spike intervals are mainly controlled by refractory periods [33], we tested if MDA prolonged ARP. The measurements of ARP were done by giving multiple pulses (Methods for details; Table S2). These results indicate that MDA attenuates the capacity of encoding sequential spikes through the prolongation of absolute refractory periods (Fig. 4).

Bottom Line:
These changes were found associated with the deterioration of encoding action potentials in cortical neurons.In addition, MDA increased the ratio of γ-aminobutyric acid to glutamate in turtle's brain, as well as the sensitivity of GABAergic neurons to inputs compared to excitatory neurons.Therefore, MDA, as a metabolic product in the brain, may weaken cerebral function during carbonyl stress through breaking the homeostasis between excitatory and inhibitory neurons.

ABSTRACTThe levels of malondialdehyde (MDA) are high in the brain during carbonyl stress, such as following daily activities and sleep deprivation. To examine our hypothesis that MDA is one of the major substances in the brain leading to fatigue, the influences of MDA on brain functions and neuronal encodings in red-eared turtle (Trachemys scripta) were studied. The intrathecal injections of MDA brought about sleep-like EEG and fatigue-like behaviors in a dose-dependent manner. These changes were found associated with the deterioration of encoding action potentials in cortical neurons. In addition, MDA increased the ratio of γ-aminobutyric acid to glutamate in turtle's brain, as well as the sensitivity of GABAergic neurons to inputs compared to excitatory neurons. Therefore, MDA, as a metabolic product in the brain, may weaken cerebral function during carbonyl stress through breaking the homeostasis between excitatory and inhibitory neurons.